MYO3A

myosin IIIA, the group of Myosin heavy chains, class III

Basic information

Region (hg38): 10:25934229-26212532

Previous symbols: [ "DFNB30" ]

Links

ENSG00000095777 ∙ NCBI:53904 ∙ OMIM:606808 ∙ HGNC:7601 ∙ Uniprot:Q8NEV4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 30 (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 30 (Moderate), mode of inheritance: Semidominant
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 30 (Strong), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 30 (Definitive), mode of inheritance: AR
• hearing loss, autosomal dominant 90 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 90; Deafness, autosomal recessive 30	AD/AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	12032315; 29880844; 32519820

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYO3A gene.

• not provided (20 variants)
• Autosomal recessive nonsyndromic hearing loss 30 (7 variants)
• Nonsyndromic genetic hearing loss (1 variants)
• MYO3A-related disorder (1 variants)
• Sensorineural hearing loss disorder (1 variants)
• nonsyndromic sensorineural hearing loss (1 variants)
• Hearing loss, autosomal dominant 90 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYO3A gene is commonly pathogenic or not. These statistics are base on transcript: . Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			9	74	5	88
missense	1		296	16	7	320
nonsense	10	5	7			22
start loss			1			1
frameshift	11	7	3			21
splice donor/acceptor (+/-2bp)	3	15	3			21
Total	25	27	319	90	12

Highest pathogenic variant AF is 0.0000525742

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYO3A	protein_coding	protein_coding	ENST00000265944	33	278261

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.81e-45	0.0000373	125367	0	381	125748	0.00152

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.132	841	830	1.01	0.0000421	10659
Missense in Polyphen		220	232.94	0.94443		3042
Synonymous	-0.947	310	290	1.07	0.0000146	2936
Loss of Function	1.23	76	88.5	0.859	0.00000468	1119

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00248	0.00247
Ashkenazi Jewish	0.000893	0.000893
East Asian	0.00125	0.00125
Finnish	0.000232	0.000139
European (Non-Finnish)	0.00151	0.00149
Middle Eastern	0.00125	0.00125
South Asian	0.00311	0.00311
Other	0.00147	0.00147

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable actin-based motor with a protein kinase activity. Probably plays a role in vision and hearing (PubMed:12032315). Required for normal cochlear hair bundle development and hearing. Plays an important role in the early steps of cochlear hair bundle morphogenesis. Influences the number and lengths of stereocilia to be produced and limits the growth of microvilli within the forming auditory hair bundles thereby contributing to the architecture of the hair bundle, including its staircase pattern. Involved in the elongation of actin in stereocilia tips by transporting the actin regulatory factor ESPN to the plus ends of actin filaments (By similarity). {ECO:0000250|UniProtKB:Q8K3H5, ECO:0000269|PubMed:12032315}.

Recessive Scores

• pRec: 0.165

Intolerance Scores

• loftool: 0.265
• rvis_EVS: 1
• rvis_percentile_EVS: 90.66

Haploinsufficiency Scores

• pHI: 0.165
• hipred: N
• hipred_score: 0.299

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.831

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Myo3a
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: visual perception;sensory perception of sound;protein autophosphorylation;response to stimulus;cochlea morphogenesis
• Cellular component: cytoplasm;myosin complex;filopodium;filamentous actin;stereocilium tip;filopodium tip
• Molecular function: microfilament motor activity;actin binding;protein kinase activity;protein serine/threonine kinase activity;protein binding;calmodulin binding;ATP binding;actin-dependent ATPase activity;ADP binding;plus-end directed microfilament motor activity